0.05).EBV-specific IgM was detected more frequently in patients than that in controls(P

Objective:To identify the pathogenic gene mutations in a family with early onset severe retinal dystrophy (EOSRD).Methods:A retrospective clinical study. One patient and three family members from a Han of EOSRD who were diagnosed at Henan Eye Hospital in August 2018 were included in the study. After the detailed history of the patients was collected, all participants underwent best corrected visual acuity (BCVA), slit-lamp, fundus biomicroscopy with the slit lamp, untra-widefield fundus color photography, spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ff-ERG). The subject’s peripheral venous blood of 5 ml was collected and the whole genome DNA was extracted. A genetic eye disease capture chip containing 441 disease-causing genes was used for targeted capture and enrichment of high-throughput sequencing, and Sanger sequencing was performed for the clear pathogenic mutation sites; the analysis software was used for bioinformatics analysis of the mutation sites.Results:A 6-year-old female proband developed poor night vision in both eyes after 1 year old. The BCVA of both eyes were 0.1. The color of the optic disc was slightly lighter; the diameter of the retinal vessels was slightly reduced, and extensive pigment changes can be seen in the retina outside the vascular arch. SD-OCT examination showed that the outer membrane, ellipsoid zone and chimera zone in the central fovea of both eyes were unclear and intermittent. The visual area outside the fovea was neuroepithelial outer plexiform layer, outer nuclear layer, outer membrane, ellipsoid zone. The chimera zone gradually disappeared, and the thickness of the pigment epithelial layer was not uniform. In ff-ERG examination, the functions of the binocular cone and rod system were severely decreased. The results of genetic testing showed that there were c.921C>A homozygous mutations in the Tubby-like protein (TULP1) gene of the proband, and c.3121C>T and c.3488G>A compound heterozygous mutations in the cyclic nucleotide gated channel beta 1 (CNGB1) gene. Amino acid conservation analysis results showed that the above three mutation sites were highly conserved in multiple species; bioinformatics analysis results showed that TULP1 gene c.921C>A (p.Cys307*) had translation termination in the protein conserved region, CNGB1 gene c.3121C>T (p.Arg1041Trp) and c.3488G>A (p.Gly1163Glu) had amino acid polarity changes in the protein conserved region, which led to major changes in the protein spatial structure.Conclusion:TULP1 gene c.921C>A homozygous mutation, CNGB1 gene c.3121C>T and c.3488G>A compound heterozygous mutation are the mutation sites of this EOSRD family.

AIM: To study the changes of mitochondrial membrane potential(△?m) and mitochondrial mass in apoptosis of Jurkat cells induced by camptothecin(CPT).METHODS: Jurkat cells were treated with CPT.Annexin V-FITC/propidium iodine(PI) double stainig was used to detected early stage of apoptosis and PI staining for analyzing the cell cycle.Jurkat cells were stained by annexin V-PE/DiOC_6(3) to detect changes of △?m.The mitochondrial mass was measured by cytometry with NAO staining.RESULTS: 6 h after treated with 10 ?mol/L CPT,the rate of early apoptotic cells(22.59?1.04)% had significantly difference compared with control group(3.93?0.73)%(P0.05).Apoptotic peak appeared obviously after treated with CPT,the percentage of late apoptotic cells(13.58?0.97)% had distinctly difference compared with control group(3.18?0.51)%(P

Objective:To initially investigate whether simultaneous radiochemotherapy with hyperthermia can prolong the survival of glioblastoma (GBM) patients.Methods:Clinical data of 61 GBM patients undergoing surgery in our hospital from September 2016 to June 2019 were retrospectively analyzed. According to different treatment methods, all patients were divided into the control group ( n=34) and observation group ( n=27). In the control group, three-dimensional radiotherapy with a dose of 60 Gy combined with temoazolamine chemotherapy was delivered. In the observation group, simultaneous radiochemotherapy with 15-20 cycles of hyperthermia at 40-41℃ was supplemented. The survival time was calculated by Kaplan-Meier method, and the survival time was compared with log-rank test between two groups. Results:The median progression-free survival in the observation group was significantly longer than that in the control group (14.33 months vs.9.94 months, P<0.05). The median overall survival in the observation group was also remarkably higher than that in the control group (18 months vs. 14 months, P<0.05). Conclusions:Simultaneous radiochemotherapy with hyperthermia is innovatively applied to treat GBM after surgical resection. Preliminary findings demonstrate that compared with chemoradiotherapy, simultaneous radiochemotherapy with hyperthermia can prolong the survival time of GBM patients.

Esophageal cancer is a malignant tumor of the digestive system that has a high incidence in China. The traditional treatment methods include surgery, radiotherapy, and chemotherapy, but the long-term efficacy is not good and the side effects are obvious. As a traditional physical therapy, hyperthermia has no significant toxic and side effects. Studies have shown that hyperthermia can increase the sensitivity of esophageal cancer to radiotherapy and chemotherapy, and its combined use in the treatment of esophageal cancer can prolong the survival and improve the quality of life. In addition, the innovation of materials and technologies brings new breakthroughs to tumor hyperthermia.

OBJECTIVETo investigate HIV infection status and its influence factors in men who have sex with men (MSM) in Sichuan province.

METHODSA face to face investigation and Syphilis and HIV serological detection were conducted among 2 783 MSM who have the insertion of oral or anal sex with men over the past year recruited by snowball sampling and respondent driven sampling methods in nine cities' Gay venues of Sichuan province. χ(2) test and logistic regression analysis were used for statistical analysis.

RESULTSA total of 2 783 MSM were surveyed, of which HIV and Syphilis infection rates were 11.1% (147/2 783) , 5.3% (310/2 783) , respectively. The HIV infection rates of <20 year-old age group, 20-29 year-old age group, 30-39 year-old age group, 40-49 year-old age group, ≥ 50 year-old age group were 6.6% (15/227), 9.7% (143/1 471), 11.8% (80/679), 18.0% (53/294), 17.0% (19/112) (χ(2) = 25.91, P < 0.05). The risk of HIV infection in 30-39 year-old age group, 40-50 year-old age group,> 50 years age group were 2.05 (1.14-3.69) times, 3.24 (1.75-6.01) times, 2.60 (1.22-5.52) times respectively of the <20 years age group. The risk of HIV infection in middle school and below one was 16.5% (73/443) , higher than the high school/college education MSM (11.1% (99/891) ) and the college and higher education MSM (9.5% (138/1 446)) (χ(2) = 16.46, P < 0.05). The risk of HIV infection in High school/college education MSM were 0.64 (0.45-0.90) times of the middle school and below. The HIV infection rates of MSM who accepted a HIV test and knew the result within the last year was 8.2% (119/1 446) , lower than the group who did not accepted any HIV test (14.3% (191/1 336) ) (χ(2) = 25.81, P < 0.05). The HIV infection rates of MSM who received intervention services was 10.1% (256/2 539), lower than the group who did not receive any intervention services (22.1% (54/244) ) (χ(2) = 32.65, P < 0.05) . The HIV infection rates of Syphilis-positive MSM was 32.0% (47/147) , higher than the Syphilis-negative one (10.0% (263/2 636) ) (χ(2) = 68.06, P < 0.05). Received intervention services (OR (95%CI) was 0.52 (0.40-0.68) ) and accepted a HIV test and knew the result within the last year (OR (95%CI) was 0.52 (0.36-0.74) ) were the protective factors of HIV infection. At the same time, the syphilis infection (OR (95%CI) was 4.01 (2.73-5.88) ) were risk factors for HIV infection.

CONCLUSIONThe prevalence rates of HIV infections were considered to be high among MSM in Sichuan province. The MSM of low-literacy, 30 years or older, not received any intervention services, not received any intervention services.Syphilis-positive have a greater risk of HIV infection.

Adolescent ; Adult ; China ; Data Collection ; Demography ; HIV Infections ; HIV Seropositivity ; Homosexuality, Male ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Sexual Behavior ; Surveys and Questionnaires ; Syphilis

Background: Insulin regulates glucose homeostasis and has important effects on metabolism, cell growth, and differentiation. Depending on the cell type and physiological context, insulin signal has specific pathways and biological outcomes in different tissues and cells. For studying the signal pathway of insulin on glycolipid metabolism in porcine embryonic fibroblast (PEF), we used high-throughput sequencing to monitor gene expression patterns regulated by insulin. Objectives: The goal of our research was to see how insulin affected glucose and lipid metabolism in PEFs. Methods: We cultured the PEFs with the addition of insulin and sampled them at 0, 48, and 72 h for RNA-Seq analysis in triplicate for each time point. Results: At 48 and 72 h, 801 and 1,176 genes were differentially expressed, respectively. Of these, 272 up-regulated genes and 264 down-regulated genes were common to both time points. Gene Ontology analysis was used to annotate the functions of the differentially expressed genes (DEGs), the biological processes related to lipid metabolism and cell cycle were dominant. And the DEGs were significantly enriched in interleukin-17 signaling pathway, phosphatidylinositol-3-kinase-protein kinase B signaling pathway, pyruvate metabolism, and others pathways related to lipid metabolism by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Conclusions These results elucidate the transcriptomic response to insulin in PEF. The genes and pathways involved in the transcriptome mechanisms provide useful information for further research into the complicated molecular processes of insulin in PEF.

Objective:To evaluate the effect of hyperthermia on the apoptosis and the expression levels of cysteine-containing aspartate-specific protease-3 (Caspase-3) and phosphorylated protein kinase B (p-AKT) in laryngeal squamous cell carcinoma cells.Methods:A prospective study was conducted on 30 patients with laryngeal squamous cell carcinoma who were treated at the First Affiliated Hospital of Zhengzhou University from October, 2021 to October, 2022. Three times of hyperthermia were performed with a time interval of 24 h. The tumor tissue samples were collected from 30 patients before and after hyperthermia and divided into before hyperthermia group (group A ) and after hyperthermia group (group B). Self-control study mode was adopted for comrparative analysis. The cell apoptosis was detected by TUNEL assay. The expression levels of Caspase-3 and p-AKT in the tissues were detected by immunohistochemistry. Positive cell ratio and immunohistochemistry (IHC) score were recorded. Comparison between two groups was performed by paired t-test. The correlation between the degree of apoptosis and the changes of Caspase-3 and p-AKT molecules was assessed by Pearson correlation analysis. Results:No evident adverse reactions were observed in 30 patients after hyperthermia. The apoptosis index of laryngeal squamous cell carcinoma cells in group A was 2.37%±1.33%, and 4.27%±3.93% in group B ( P=0.006). In group A, the ratio of Caspase-3 positive cells in tumor tissues was 62.31%±19.49% and 80.79%±17.15% in group B ( P=0.001). The ratio of p-AKT positive cells in group A was 31.26%±19.30%, and 26.26%±15.86% in group B ( P=0.023). There was a positive correlation between the degree of apoptosis and the changes of Caspase-3 molecule ( r=0.544, P=0.002), but a negative correlation was noted between the degree of apoptosis and the changes of p-AKT molecule ( r=-0.434, P=0.017). Conclusion:Hyperthermia can promote the apoptosis of tumor cells in laryngeal squamous cell carcinoma, which may be related to Caspase-3 dependent apoptosis, and the inhibition of AKT phosphorylation is also involved in this process.

Objective:To determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type.Methods:A retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis.Results:The BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene ( CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. Conclusion:CACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.

Objective:To identify the pathogenic gene mutations in a family with Leber congenital amaurosis (LCA).Methods:In October 2018, 1 patient and 3 normal family members from a LCA family was enrolled in this retrospective study. Detailed medical history of proband was obtained and fixation test, cycloplegic refraction, slit-lamp, fundus color photography and full-field ERG were performed. And other family members underwent BCVA, refraction slit-lamp, fundus biomicroscopy with the slit lamp, fundus color photography and full-field ERG. The family was investigated with a specific hereditary eye disease enrichment panel which contained 441 known pathogenic genes and based on targeted exome capture technology first to indentify the potential pathogenic genes and mutations. Then the potential pathogenic mutations were conformed by Sanger sequencing. Finally, the results were analyzed via bioinformatics analysis.Results:The proband showed no trace object from childhood, but had obvious photophobia and nystagmus. No positive changes were found in the anterior segment, vitreous and retina in both eyes. Both cone and rod system function decreased significantly in full-field ERG in both eyes. Gene tests showed the proband carried both RPGRIP1 c.1635dupA and c.3565C> T, which composited a heterozygous mutation. Bioinformatics analysis showed RPGRIP1 c.1635dupA was a pathogenic mutation, and RPGRIP1 c.3565C> T which was a novel potential pathogenic mutation in LCA.Conclusion:The compound heterozygous mutation, c.1635dupA and c.3565C> T in RPGRIP1 may be responsible for the pathogenesis in this Chinese Han LCA pedigree.